We have recently shown that there is a substance excreted by the kidneys of laboratory rabbits and human beings which, when injected into the laboratory rabbit, or prevented from being excreted (in nephrectomized rabbits or in hemodialysis patients with partial renal function), results in a fall in body temperature and an attenuation of pyrogen-induced fever. We have called this substance "endogenous cryogen" (EC) since it not only is an effective antipyretic but also reduces normal resting body temperature. EC has been characterized by ultrafiltration to be between 10,000 and 50,000 daltons and by gel filtration to be approximately 36,000 daltons. EC is destroyed by heating to 97 degrees C and by the proteolytic enzyme trypsin. Several important questions remain to be answered about EC. Where is the site of action of EC? Does the excretion of EC vary during fever, time of day, during exercise, etc.? Does EC have a physiological role in the regulation of body temperature during health and disease? The specific aims of this research proposal are to answer the above questions about this newly discovered and potentially important naturally occurring cryogen.